SASH1 (SAM and SH3 domain containing 1)

2013-08-01   Klaus-Peter Janssen 

Department of Surgery, Technische Universitaet Muenchen, Ismaninger Str 22, 81675 Munich, Germany





Entrez Gene: 23328 C, Ensembl: ENSG00000111961 C, UCSC: uc003qme.1 D, Vega:OTTHUMG00000015773.
Atlas Image
Schematic Structure of the Exon structure of human SASH1, as compared to the other members of the SLY-family of signal-adapter proteins, SLy1 (SH3-protein expressed in lymphocytes), and SAMSN1 (or SLy2). At the bottom, the transcribed full-length protein is shown schematically. SASH1 is the largest member of the protein family, it is encoded by 20 exons. All SLY-family proteins share a central conserved NLS (nuclear localisation signal) sequence, a SH3 and a SAM domain (dotted line). SASH1 comprises, in addition, a coiled-coil (CC) motif, a N-terminally located NLS signal (NLS2), a poly-prolin motif (PPP), and a second SAM domain at the C-terminus.


SASH1: located on human chromosome 6. Detailed gene locus: 6q24.3: 148593440-148873186 (forward strand).
ENSEMBL Database: Gene ID: ENSG00000111961.


20 Protein-coding transcribed Exons, 7700 bp transcript, encoding 1247 amino acid residues.


No known pseudogenes.



Human SASH1 is comprised of 1247 amino acid residues, with a pI of 5.7, and a molecular mass of 137 kDa (please note that the apparent mass on denaturing SDS-PAGE is higher, roughly 170 kDa). SASH1 contains the following domains (from amino- to carboxyterminus): a predicted short coiled-coil stretch (CC), two predicted nuclear localisation signals (NLS1 and NLS2), a Src-homology-3 domain (SH3, aa 557 - aa 614), a first sterile alpha motif (SAM1, aa 633 - aa 697), a proline-rich sequence (PPP, aa 978 - aa 1059), and a second sterile alpha motif domain (SAM2, aa 1177 - aa 1241).
Atlas Image
Diagram schematically depicts human SASH1 protein (1247 aa), and the above-mentioned sequence-features: coiled-coil stretch (CC), nuclear localisation signals (NLS1 and NLS2), Src-homology-3 domain (SH3), a sterile alpha motif (SAM), a proline-rich sequence (PPP).


Human SASH1 was first described in 2003 as putative tumor suppressor in breast cancer, it encodes a protein with both cytosolic and nuclear localisation. It lacks enzymatic activity, but, due to its multiple protein-protein interactions domains (SH3, SAM, poly-prolin stretches), it is likely to serve as a signal-adapter module that integrates and coordinates other proteins, thereby acting as a negative/positive signal transduction nodule.


SASH1 shows broad expression on protein level in human tissue and cell lines, as well as in mouse tissue. Exception: no or only weak expression has been found in lymphocytes.


SASH1 is found both in the cytosol, as well as in the nucleus, with the exception of the nucleolus. Enrichment in membrane-proximal areas in migrating cells at the lamellipodia (Martini et al., 2011).


SASH1 has no intrinsic enzyme activity, but can form multi-protein complexes due to its protein-protein interaction domains, and can modulate intracellular signal transduction. Moreover, SASH1 is implicated in the regulation of cell adhesion and migration (Martini et al., 2011).


SASH1 belongs to the SLY-family, closest homologues: SLy1 and SLy2 (SH3-domain containing protein expressed in lymphocytes). Of note, SLy1 and SLy2 are much smaller (around 380 aa), and SLy1 is exclusively expressed in lymphocytes.



Heterozygous germline mutations have been identified in the three nonconsanguineous families with benign dermatologic features in a Chinese study (Zhou et al., 2013). However, no correlation between these mutations and occurrence of malignoma has been reported so far:
1) T → G substitution at nucleotide 2126 (TAC → GAC) in exon 14, resulting in amino acid substitutions of Tyr to Asp (Y551D) at codon 551
2) T → C substitution at nucleotide 2019 (CTC → CCC) in exon 13, resulting in Leu to Pro at codon 515 (L515P)
3) G → A substitution (GAA → AAA) at position 2000 in exon 13, causing Glu to Lys at codon 509 (E509K).


No truncating or nonsense mutations have been identified in somatic cells for SASH1 in a study on human breast cancer (Zeller et al., 2003).

Implicated in

Entity name
Breast cancer
Loss of the gene-internal microsatellite DNA marker D6S311 was found in 30% of samples of primary breast carcinoma, and the LOH was significantly correlated with poor survival and increase in tumor size. In established human mammary cancer cell lines, SASH1 is expressed at relatively low levels. SASH1 is downregulated in the majority (74%) of breast tumors in comparison with corresponding normal breast epithelia. In addition, SASH1 is also downregulated in tumors of the lung and thyroid. (Zeller et al., 2003).
Entity name
Colorectal cancer
The mRNA as well as protein expression of SASH1 was strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in colorectal liver metastases. In contrast, SASH1 expression was not significantly altered in benign adenomas and in early stage lesions (UICC I). Around 40% of primary colon tumours tested (n=113) showed a 10-fold or stronger reduction in SASH1 expression, compared to normal colon mucosa. Decreased SASH1 mRNA expression was correlated with the occurrence of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival (Rimkus et al., 2006). Recently, these results were confirmed on an independent patient collective of stage II colon cancer (n=179 patients), confirming that decreased SASH1 expression is an independent negative prognostic factor in colon cancer, allowing to distinguish high-risk patients in early, locally restriced stages of the disease (Nitsche et al., 2012).
Entity name
Pancreatic cancer (unpublished observations)
In a collective of n=103 patients with pancreatic ductal adenocarcinoma, 38% of the tumors showed no or strongly reduced SASH1 protein expression by immunohistochemistry. Decreased SASH1 expression was significantly reduced with poor survival in Kaplan-Meier analysis (Tiago de Oliveira and Klaus-Peter Janssen, unpublished data).
Entity name
Benign dyskeratosis
SASH1 germline mutations have been identified in patients with a kind of dyschromatosis. Of note, three independent heterozygous germline mutations have been identified, that cause amino acid substitutions in the central SH3/SAM-containing region in the SASH1 gene. In epidermal tissues from an affected individual, increased transepithelial migration of melanocytes was observed (Zhou et al., 2013).
Entity name
SASH1 protein was significantly down-regulated in osteosarcoma tissues compared to normal bone tissue. Moreover, SASH1 protein showed significant down-regulation in osteosarcoma tissues from patients with lung metastasis compared to those without lung metastasis, and, lastly, a gradual decrease of SASH1 expression occurred with increasing Enneking stage (Meng et al., 2013).


Pubmed IDLast YearTitleAuthors
224882442012Effects of SASH1 on lung cancer cell proliferation, apoptosis, and invasion in vitro.Chen EG et al
230237272012Effects of SASH1 on melanoma cell proliferation and apoptosis in vitro.Lin S et al
218205262011The candidate tumor suppressor SASH1 interacts with the actin cytoskeleton and stimulates cell-matrix adhesion.Martini M et al
231087922013SASH1 regulates proliferation, apoptosis, and invasion of osteosarcoma cell.Meng Q et al
230956202012Integrative marker analysis allows risk assessment for metastasis in stage II colon cancer.Nitsche U et al
170889072006Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer.Rimkus C et al
229152662012Overexpression of SASH1 related to the decreased invasion ability of human glioma U251 cells.Yang L et al
127719492003SASH1: a candidate tumor suppressor gene on chromosome 6q24.3 is downregulated in breast cancer.Zeller C et al
233332442013SASH1 regulates melanocyte transepithelial migration through a novel Gαs-SASH1-IQGAP1-E-Cadherin dependent pathway.Zhou D et al

Other Information

Locus ID:

NCBI: 23328
MIM: 607955
HGNC: 19182
Ensembl: ENSG00000111961


dbSNP: 23328
ClinVar: 23328
TCGA: ENSG00000111961


Gene IDTranscript IDUniprot

Expression (GTEx)


Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
127719492003SASH1: a candidate tumor suppressor gene on chromosome 6q24.3 is downregulated in breast cancer.47
170889072006Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer.32
189786782008Candidate gene/loci studies in cleft lip/palate and dental anomalies finds novel susceptibility genes for clefts.21
231087922013SASH1 regulates proliferation, apoptosis, and invasion of osteosarcoma cell.17
218205262011The candidate tumor suppressor SASH1 interacts with the actin cytoskeleton and stimulates cell-matrix adhesion.16
229152662012Overexpression of SASH1 related to the decreased invasion ability of human glioma U251 cells.15
263508782016Genome-wide association study for rotator cuff tears identifies two significant single-nucleotide polymorphisms.13
271788182016Overexpression of SASH1 Inhibits TGF-β1-Induced EMT in Gastric Cancer Cells.13


Klaus-Peter Janssen

SASH1 (SAM and SH3 domain containing 1)

Atlas Genet Cytogenet Oncol Haematol. 2013-08-01

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